For years, physicians have treated systemic juvenile idiopathic arthritis – a serious, complex, but rare disease – based on limited scientific data and their own experience. But recently, as the number of effective medicines to control systemic juvenile idiopathic arthritis, or sJIA, have increased, an organization of leading pediatric rheumatologists has decided that sJIA treatment should be standardized. By establishing treatment plans, the physicians hope patient care will improve and future research will be made easier.
“The Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis” – published in July 2012 in the journal Arthritis Care & Research – was assembled by a core workgroup from the Childhood Arthritis and Rheumatology Research Alliance, or CARRA, a clinical research network whose more than 300 members are affiliated with 92 centers in North America.
“There is wide variation in therapeutic approaches to [sJIA],” the project authors write. “Understanding the comparative effectiveness of the diverse therapeutic options available for treatment … can result in better health outcomes” for patients.
Systemic JIA is distinguished from other forms of JIA by serious inflammation in the bloodstream that can affect internal organs and cause high fevers and rashes. Of the approximately 300,000 children with juvenile arthritis in this country, an estimated 10 percent have sJIA.
The biologic tocilizumab, or Actemra, an IL-6 inhibitor, was the first treatment approved by the U.S. Food and Drug Administration, or FDA, for sJIA in April 2011. Anakinra, or Kineret, an IL-1 inhibitor, is FDA-approved to treat adult rheumatoid arthritis, but is sometimes used “off-label” for sJIA. Other IL-1 inhibitors, such as canakinumab, or Ilaris, and rilonacept, or Arcalyst, are currently in clinical trials to treat sJIA. Biologic drugs already approved for JIA may not be as effective in the treatment of sJIA.
Although the American College of Rheumatology last April issued recommendations for treating all forms of JIA – before Actemra was approved for sJIA – the CARRA plans aim to further refine treatment approaches for sJIA. The authors hope the four plans presented in the article will help standardize care for children newly diagnosed with sJIA through the first nine months of treatment.
The four plans cover the use – in combination or alone – of four therapeutic agents: corticosteroids, the disease-modifying methotrexate and the biologics anakinra and tocilizumab.
“There has been a medication revolution in arthritis treatment since the introduction of biologics,” says co-author Yukiko Kimura, MD, chief of pediatric rheumatology at Joseph M. Sanzari Children’s Hospital, Hackensack University Medical Center, in New Jersey, who lead development of the consensus treatment plans with co-author Esi Morgan DeWitt, MD, associate professor, Department of Pediatrics at Cincinnati Children's Hospital Medical Center. “We have learned that starting to treat with these medications very early may dramatically change the course of a disease that otherwise can be so terribly crippling and disabling and, in the case of systemic JIA, life-threatening.”
They also hope the treatment plans serve as the basis for comparative studies of sJIA therapies. “For the first time, we are trying to persuade pediatric rheumatologists to reduce variations in treatment so we can obtain accurate data on the outcomes and long-term safety of sJIA therapies,” says Carol A. Wallace, MD, professor of pediatrics at the University of Washington School of Medicine and Seattle Children's Hospital and one of the co-authors of the article.
Usually, physicians develop treatment guidelines for diseases – such as diabetes or various cancers – based on mountains of data. But in the case of sJIA, those mountains don’t exist.
Dr. Wallace says because there isn’t enough data, no one can determine which treatments are the best; information has to come from the field. “Everyone has an opinion and a particular method and approach, but none of it is evidence-based,” she says.
To arrive at the four treatment plans, the authors collected information about how most pediatric rheumatologists treat sJIA. They then tried to standardize the information using “consensus methodology” so that “everyone who participated felt that what was being recommended in each of the plans was close to normal practice,” explains Dr. Kimura.
The advantage of establishing the treatment plans by consensus within the CARRA network is that it will increase the likelihood that pediatric rheumatologists will follow them.
The consensus process, says Dr. Wallace, is the same process the Children's Oncology Group used to standardize and improve treatment for childhood acute leukemia decades ago.
“Every child who received cancer treatment was entered in a database, and the results of one treatment method were compared with those of another method and then another in a [repetitive] approach in order to gather evidence for the best standardized therapies for each kind of leukemia,” she explains.
“As a result, the treatment approaches to childhood cancer evolved in a data-driven way, and 80 percent of children with acute leukemia now have a five-year disease-free survival rate.”
The researchers keep the CARRA Registry, a database of patients with childhood rheumatic diseases, that will be used to collect data for sJIA research as well as for other projects, including upcoming consensus treatment plans for another type of JIA called pediatric polyarticular arthritis. The Arthritis Foundation is the founding and ongoing funder of the database and infrastructure of the CARRA Registry. It will also fund the creation of pilot programs for the sJIA treatment plans at select CARRA-associated university and pediatric medical centers.
“This will help us see how well the plans perform, how easy they are to use and what problems arise when pediatric rheumatologists try to use them as part of daily clinical practice,” Dr. Kimura says.
Once any clinical problems have been solved, the goal is to extend the pilot programs to all of the sites in the CARRA registry. Dr. Kimura says, “We want to gather information on many more patients with sJIA so we can compare the effectiveness of different treatments over time.”
Dr. Wallace stresses that the consensus treatment plans are not just for CARRA physicians. “They are intended for all providers caring for children with sJIA, including international pediatric rheumatologists and even adult rheumatologists,” Dr. Wallace says. “We want to see all physicians treating childhood arthritis more uniformly. A culture of research is key because it's the only way we can keep moving forward and improve the care that patients receive.”
[Last reviewed/updated 7.8.14]